The ability of cells to respond to each other and substrata (forms of cell social behavior) is an important part of normal growth and development. Alterations in these responses are displayed by various tumor cells and are believed to be involved in metastasis, changes in cell adhesion and the loss of contact inhibition of growth. The possible involvement of the cell surface molecule heparin sulfate proteoglycan (HSPG) in these responses has received support from a wide range of experimental evidence. However, despite these various data, the physiological function(s) of this interesting molecule remains unproven. My continuing study of the structure/function relationships of cell surface HSPG will employ two major approaches: (1) protein and carbohydrate chemical analyses to further explore the molecular organization of the HSPG molecule and (2) a novel application of existing methodology to isolate animal cell mutants defective in their ability to produce cell surface HSPG in order to establish model systems in which the physiological functions of HSPG can be more precisely determined. It is expected that information from the study of such mutants will better define the role of HSPG in normal and pathological states. (A)